Thrombin Effects on Astrocytes: Autonomic Failure in Trauma, Burns, and Infection

Historically, astrocytes had been thought to perform principally maintenance functions within the brain. However, studies have now revealed the active role astrocytes play in the regulation of neuronal excitability and synaptic communications within neural circuits. This function is especially important to the control of autonomic mechanisms that are regulated by the hindbrain. Astrocytes enmeshed within the important autonomic regulatory circuits are now considered critical to the proper function of hindbrain circuits controlling glycemia, gastrointestinal, and cardiorespiratory functions. Recently, hindbrain astrocytes have also been implicated in pathophysiological changes in autonomic function associated with severe trauma, burns and systemic infection. A common factor in these pathological insults is the generation of significant levels of circulating thrombin. Physiological studies show that thrombin powerfully activates hindbrain astrocytes in critical autonomic control circuits that trigger drastic and, possibly, lethal effects. Such an interaction may help explain why COVID-19 infections, which produce disseminated thrombosis, can predispose patients to severe hyperglycemia and respiratory arrest.